Abstract Exposure to maternal depression in early life increases the risk of socioemotional and cognitive (SEC) problems in childhood and over the lifecourse. This has led to the promotion of depression treatment as a critical early childhood intervention. However, there is insufficient evidence on whether depression treatments alone reduce offspring risk in low resource settings where other social and economic adversities are highly prevalent. The proposed study in rural Pakistan will, first, examine the impact of a cluster randomized intervention, extended to include both maternal depression and child development components, on child SEC outcomes at ages 5-8. Second, we will closely examine the psychosocial and biological processes through which maternal depression and other adversities lead to emerging SEC difficulties by continuing to follow the mothers and children, currently in our study from birth to age three, through early primary school years. Preliminary findings from our current study, consisting of a cluster-RCT examining the impact of a perinatal maternal depression intervention on child development within a population representative birth cohort design, have yielded several insights: (1) the ?Thinking Healthy Program - Peer delivered? (THPP) shortened the initial maternal depression episode but its longer term impact is unclear; (2) although the THPP did not have an observable impact on SEC outcomes through age 2, it did favorably impact markers of hypothalamic?pituitary? adrenal (HPA)-axis function in children at 12 months of age; and (3) exposure to adversities (acute poverty, intimate partner violence (IPV), and low maternal social support) appear to be more impactful on child outcomes than maternal depression during the earliest developmental period, and child sex may influence the prevalence of certain adversity exposures after birth as well as their impact on child outcomes. The children of this cohort are about to embark on their first major life transition requiring significant adaptation ? that into formal schooling. Following the children through this transition allows us to test key hypotheses linking the rich data already collected on multiple adversities beginning in pregnancy, potential psychosocial and biological mechanisms, and outcomes at this important stage of life course. This study will continue to follow our unique cohort until the children turn 8. The specific aims of the proposed study are to: (1) evaluate the impact of the ongoing and extended intervention (now called ?THP Preschool? (THP-PS) on child socioemotional and cognitive (SEC) outcomes at ages 5 through 8, and determine the extent to which the impact is mediated by maternal depression trajectories; (2) examine how the type and timing of adversity exposures, including maternal depression, impacts HPA-axis dysregulation in children, and whether HPA-axis indicators mediate the effect of adversity exposures on child SEC indicators. As part of this aim we will also examine the impact of the ongoing intervention on child HPA-axis biomarkers; and (3) explore, through quantitative and qualitative inquiry, emerging child sex differences in exposure to adversities and their effects on child outcomes.